Title: P-POD
1P-POD
- The Princeton Protein Orthology Database
- Literature Discussion
- Tim Hulsen 2008-05-08
2P-POD - Manuscript
- The Princeton Protein Orthology Database (P-POD)
a comparative genomics analysis tool for
biologists - Heinicke S1,, Livstone MS1,, Lu C1,, Oughtred
R1,, Kang F1, Angiuoli SV2,3, White O2, Botstein
D1, Dolinski K1 - PLoS ONE. 2007 Aug 22 2(1) e766
- PubMed ID 17712414
- 1 Lewis-Sigler Institute for Integrative
Genomics, Princeton University, Princeton, New
Jersey, United States of America. - 2 The Institute for Genomic Research, Rockville,
Maryland, United States of America - 3 Center for Bioinformatics and Computational
Biology, University of Maryland, College Park,
Maryland, United States of America - These authors contributed equally to this work
3P-POD - Introduction
- Existing many biological databases that provide
comparative genomics information and tools - None of these combine results from multiple
comparative genomics methods with manually
curated information from the literature - ? P-POD Princeton Protein Orthology Database
- Visualizes phylogenetic relationships among
predicted orthologs - Shows the orthologs in a wider evolutionary
context - Contains experimental results manually collected
from the literature, that can be compared to the
computational analyses - Shows links to relevant human disease and gene
information via the OMIM, model organism and
sequence database
4P-POD Ortholog methods
- Orthology is determined using OrthoMCL
- Can be run on multiple species at once
- One of the better performing algorithms in terms
of sensitivity and specificity (Alexeyenko et
al., 2006 and Chen et al., 2007) - Evolutionary context is determined using Jaccard
- Clustering algorithm to find related proteins
- Larger groups than just orthologs
- Manuscript in preparation
5P-POD Covered species
- P-POD contains 8 species
- Plasmodium falciparum
- Homo sapiens
- Drosophila melanogaster
- Mus musculus
- Arabidopsis thaliana
- Caenorhabditis elegans
- Danio rerio
- Saccharomyces cerevisiae
- ?Most widely studied organisms, from a wide
evolutionary range
6P-POD Source Species Databases
7P-POD Supported identifiers
Organism Source Database Valid gene/protein identifier(s) Examples
P.falciparum PlasmoDB PlasmoDB ID PF08_0034
H.sapiens ENSEMBL ENSEMBL peptide ID, peptide name ENSP00000266970, CDK2
D.melanogaster FlyBase FlyBase ID CG17520-PA, CkIIalpha-PA
M.musculus ENSEMBL ENSEMBL peptide ID ENSMUSP00000068896
A.thaliana TAIR TAIR identifier or gene name AT1G25490.1, PAB4
C.elegans WormBase WormBase identifier or gene name C09G4.1, dbr-1
D.rerio ENSEMBL ENSEMBL peptide ID, ZFIN ID ENSDARP00000007117, ZDB-GENE-040808-60
S.cerevisiae SGD ORF name or gene name YNL098C, DPM1
OMIM IDs
8P-POD Orthology and clustering numbers
- 25,271 OrthoMCL families
- 15,050 Jaccard Clustering families
- 165,970 proteins (154,736 OrthoMCL and 152,799
Jaccard) - 984 families containing proteins in all species
(omnipresent) - 112 families with exactly one protein in each of
the 8 species involved in core biological
processes, such as - Translation
- Transport
- Cell cycle regulation
- Cytoskeleton organization
9P-POD Proteins in families, and orphans
- Relatively low percentages of orphans (lt13,
except for S. cerevisiae and P. falciparum) - These numbers confirm the high conservation of
proteins across eukaryotes, with the notable
exception the Plasmodium outlier - Yeast complete protein set used, including 800
ORFS flagged as Dubious by SGD. If these are
excluded, the percentage of orphans drops to 20
10P-POD Compared to other orthology databases
Tot.
2
1
2
1
2
1
1
2
4
11P-POD - Pipeline
12P-POD Pipeline Components
4 Li L, Stoeckert CJ Jr, Roos DS (2003)
OrthoMCL identification of ortholog groups for
eukaryotic genomes. Genome Res 13 21782189 5
Thompson JD, Higgins DG, Gibson TJ (1994) CLUSTAL
W improving the sensitivity of progressive
multiple sequence alignment through sequence
weighting, position-specific gap penalties and
weight matrix choice. Nucleic Acids Res 22
46734680 29 Samuel Lattimore B, van Dongen S,
Crabbe MJ (2005) GeneMCL in microarray analysis.
Comput Biol Chem 29 354359
13P-POD The Database
- P-POD uses the Generic Model Organism Database
(GMOD) database package using PostgreSQL software - GMOD is the Generic Model Organism Database
project, a collection of open source software
tools for creating and managing genome-scale
biological databases. You can use it to create a
small laboratory database of genome annotations,
or a large web-accessible community database.
GMOD tools are in use at many large and small
community databases - Other popular GMOD tools are Apollo (Genome
annotation editor), Gbrowse (Genome annotation
viewer), Cmap (Comparative map viewer), Sybil
(Comparative genome viewer), Chado (Biological
database schema) and BioMart (Data mining system)
14P-POD - Web Interface (1)
- The web interface allows users to search and
browse the data in several ways - Results can be queried by various peptide
identifiers or gene names - Searches generate result pages that contain
- a hyperlinked phylogenetic tree of predicted
orthologs generated by OrthoMCL or of more
distantly-related proteins generated by Jaccard
clustering - a list of diseases and genes associated with the
human ortholog(s) as documented in OMIM - a manually curated list of papers with
cross-complementation experiments involving the
yeast ortholog(s), from SGD database - a downloadable ClustalW alignment of family
members - Web address http//ortholog.princeton.edu
15P-POD WebInterface(2)
INPUT
OrthoMCL
OMIM
SGD Lit.
CLUSTALW
16P-POD WebInterface(3)
SGD Lit.
CLUSTALW
JACCARD
17P-POD Comparison of methods
- Orthology/clustering methods OrthoMCL and Jaccard
can be compared using P-POD - Jaccard is far more inclusive than OrthoMCL
- Shown at the right OrthoMCL family of the alpha
tubulins. It contains only the alpha tubulins,
while the Jaccard family contains the alpha,
beta, and gamma tubulins
18P-POD Discussion (1)
- P-POD shows direct orthology (OrthoMCL) and
broader evolutionary clustering (Jaccard) - P-POD uses a generic, modular database schema
(GMOD) in combination with a freely available
database system (PostgreSQL) - P-POD provides experimental evidence of
conservation curated from the primary literature - Three sets of users
- Molecular biologists that query the database over
the web to browse orthology data for their
favorite proteins - Model organism database developers, who will
quickly be able to provide comparative genomics
tools with their species of interest by
implementing our system - Computational biologists who are developing novel
comparative genomics algorithms will find the
curated information and computational data from
other methods extremely useful in assessing their
approach
19P-POD Discussion (2)
- P-POD can be downloaded in its entirety for
installation on ones own system - Software developers can use the P-POD database
infrastructure when developing their own
comparative genomics resources and database tools
20P-POD Future plans
- Provide regular updates to the data contained
within the database - Add new features to the web interface
- Expand upon the amount of data stored within the
database - Provide curated literature describing
experimental confirmation of orthology - Include literature from other species than just
S. cerevisiae - As more refined methods for automatic detection
of orthology are developed, they can be
incorporated into the P-POD tool, taking
advantage of the modular design scheme